The potential effectiveness of a boric acid gel and a 0.25% chlorhexidine gluconate (CHG) gel as vaginal microbicides were assessed. The boric acid gel was compared with a placebo gel (containing no boric acid) for effects on the vaginal ecosystem. After the monkeys received a single application of either gel, no deleterious effects were noted by colposcopy during a one-week follow up. Monkeys receiving boric acid showed an increase in lactobacilli, a beneficial microorganism in the vaginal ecosystem. Levels remained elevated for two days. No other significant microbiological changes were noted after application of either gel. Then the anti-chlamydial effects of 0.25% CHG were assessed in this model. A single application of 0.25% CHG was followed by an intravaginal inoculation with Chlamydia trachomatis in a group of monkeys, while positive control animals were inoculated with Chlamydia without pretreatment with CHG. Animals were examined by modified colposcopy, and cervical and vaginal swabs were collected for detection of Chlamydia and vaginal microflora for two weeks after inoculation. Evidence of chlamydial infection was not detected in any of the animals pretreated with 0.25% CHG, whereas all positive controls were infected. Changes in vaginal flora were minimal and transient in all animals. Colposcopic observations also showed minimal and transient changes to the vaginal epithelium in a small subset of animals.